Homeostasis and the functional roles of CD4⁺ Treg cells in aging

An upward trend in life expectancy has been observed in a majority of developed countries and leading to increasing in aging-related diseases. Aging is a risk factor for the development of widespread clinical conditions such as cardiovascular and autoimmune diseases, cancer, infections. Although studies have been very active, the problem of aging still remains one of the most obscure aspects of human biology. Regulatory T (Treg) cells with immunosuppressive properties have a pivotal role in the maintenance of immune homeostasis. Alterations in Treg cell functionality appear to be of great importance in the development of immune senescence and contribute to increased susceptibility to immune-mediated diseases with age.

This review highlights recent findings regarding the age-related changes in the numbers and functional activity of human Tregs. Some of the mechanisms that maintain the balance of Tregs during human aging are discussed. The possible roles of Tregs in the pathogenesis of diseases associated with advanced age are also considered.

Age-related systemic changes, such as thymic involution, hormonal status, and epigenetic modifications, may affect the state of the Treg population and trigger various diseases. These changes involve decline or amplification in the functional activity of Tregs, an increase in the memory Treg subset and shifting of a Th17/Treg balance.

Taken together, the reviewed data suggest equal or even increased Treg functionality with age. Thus, age-mediated Treg expansion and higher Treg activity may contribute to elevated immune suppression and increased risk of infections and cancer.